Summary: Core D Animals The Animal Core is central to the Program Project, performing bioassay experiments for Projects 1, 2, 3 and 4, and supplying tissues to the Neuropathology core (Core C), and tail biopsies to the Science core (Core B) for screening. The Animal Core will provide the following services: the highest quality animal and veterinary care; breeding of transgenic and knockout mice; experimental inoculations, and neurologic scoring of animals; bioluminescence imaging; behavioral assessments; tissue collection and storage; transportation of animals and tissues between the animal facility and the laboratory; microinjection of DNA constructs to generate new transgenic lines; and cryopreservation of new transgenic mouse lines. The demonstration that inoculation of A and tau aggregates can initiate self-propagation in the appropriate mouse model is a clear analogy to the prion diseases. However a major limitation of the A and tau inoculation models is that the mice don't show any overt clinical signs, and the only way of determining the degree of disease progression is to remove the brain for biochemical and neuropathological analysis. Our pioneering work in the field of bioluminescence imaging (BLI) and near infrared (NIR) fluorescence imaing has allowed us to address this issue and monitor disease progression in vivo. We have developed transgenic mouse models incorporating a luciferase reporter, enabling monitoring by BLI, for propagation of the prion protein (PrP) and A, and NIR fluorescent ligands that bind to tau. These provide a suite of tools to determine the biological relevance of protein and peptide aggregates formed in the Projects of this grant.